Effects of the allosteric regulators at P2X7 receptors are species-dependent. See Michel et al. (2008) [64] for an explanation. No affinity data has been published quantifying the complex interaction of GW791343 with the P2X7 receptor. We have included the interaction in the table above based on extensive experimental evidence provided in [63] and [64]. Polymyxin B is a P2X7 receptor PAM [35].

Immunopharmacology Comments

The P2X7 receptor is involved in NLRP3-type inflammasome formation, and subsequent maturation of IL-1β [60,78]. In human mast cells P2X7 receptor activation causes degranulation and inflammatory mediator release [98], and in mouse mast cells induces IL-6 and TNF-α production [60]. Studies in mice suggest that ATP released from damaged airway tissue engages the P2X7 receptor/pannexin-1 axis, leading to IL-1β maturation and pulmonary fibrosis.[79]. P2X7 receptor antagonism has also been posited as a potential pharmaceutical intervention to treat the salivary gland inflammation and sequelae of Sjögrens syndrome [57].

P2RX7 is expressed by most immune cells. It elicits an immune response when activated by extracellular ATP that is released by infected or injured cells. P2RX7 expressed on T cells is involved in proliferation, cytokine production, Th17 and T follicular helper cell differentiation and inhibition of Treg differentiation.

P2X7B: C-terminally truncated form of the full length P2X7A. This variant is due to transcription of the intron between exons 10 and 11. This inclusion introduces a new stop codon and modifies the last C-terminal 18 amino acids. GenBank accessions are AY847298 (nucleotide) and AAX82087.1 (protein).

The role of P2X7 receptor in cancer is discussed in [23-25]. The crystal structure of the truncated (lacking 240 C-terminal residues) P2X7 receptor from giant panda (Ailuropoda melanoleuca) has been resolved. This has allowed identification of the mechanism of action of several widely used antagonists [53]. Recent crystallographic data suggest that three antagonists (A740003, A804598, JNJ-47965567) previously classified as competitive inhibitors are in fact allosteric, non competitive, inhibitors [53].